Lyme disease is caused by the spirochete Borrelia burgdorferi. This zoonosis is the most prevalent vector borne infectious disease in the United States and Europe and it continues to grow geographically. The enzootic cycle of this pathogen requires that Ixodes spp. acquire B. burgdorferi from infected wildlife reservoirs and transmit it to other uninfected wildlife. At present, there are no effective measures to control B. burgdorferi; there is no human vaccine available, and, existing vector control measures are generally not acceptable to the public. However, if B. burgdorferi could be eliminated from its reservoir hosts and from the ticks that feed on them, the enzootic cycle would be broken, and the incidence of Lyme disease would decrease. To accomplish this, we developed an OspA-based bait vaccine and demonstrated that, in the Lyme disease mouse model, ad libidum feeding induced systemic anti-OspA IgG and protected all vaccinated mice from B. burgdorferi infection after tick challenge. In addition, these anti-OspA antibodies cleared B. burgdorferi from the tick vector. Thus, this bait vaccine is a good candidate to break the enzootic cycle of this pathogen. The major goal of this Phase I SBIR proposal is to test a bait vaccine by ad libidum feeding of the natural host reservoir of this spirochete, the white-footed mouse, Peromyscus leucopus. After treatment, we will assess vaccine efficacy by analyzing B. burgdorferi infection prevalence of the host and of the tick vector. We will carry out experiments both in the laboratory and in the wild. The fieldwork component of this project will be performed at the Institute for Ecosystem Studies (IES) in Millbrook, NY. In a subsequent Phase II SBIR proposal, we would expand our field studies to span the two-year life cycle of the tick vector and assess different vehicles for bait delivery. Lyme disease is the most prevalent vector borne infectious disease in the United States and Europe, and its geographical range is expanding. One way to reduce the incidence of Lyme disease is to eliminate B. burgdorferi from its reservoir and/or from the ticks that feed on them, breaking the mouse-tick cycle. The goal of this Phase I SBIR proposal is to test a bait vaccine against B. burgdorferi via ad libidum feeding of the major host reservoir of this spirochete, the white-footed mouse. [unreadable] [unreadable] [unreadable]